Safety and Tolerability of Initiating Maximum-Dose Sacubitril-Valsartan in Patients on Target Dose Renin-Angiotensin System Inhibitors

Abstract

Aim. Sacubitril-valsartan has proven beneficial in heart failure with reduced ejection fraction. Guidelines recommend initiating half-dose sacubitril-valsartan before up-titration even to patients already on target dose angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB). To reduce the number of titration steps needed in order to simplify for the patient as well as the clinic, we aimed to investigate the safety and tolerability of switching patients on target dose ACE inhibitors or ARBs directly to maximum-dose sacubitril-valsartan. Methods. This prospective cohort study was conducted between April 2016 and November 2017. A total of 66 patients with heart failure and reduced ejection fraction already on guideline-recommended target dose ACE inhibitors or ARBs (equivalent to enalapril 10 mg twice daily) were switched to maximum-dose sacubitril-valsartan (200 mg twice daily). The patients were followed for twelve months. Results. Patients had a mean age of 72 ± 10 years, mean systolic blood pressure of 121 ± 17 mmHg, and 92% were male. At 12-month follow-up, nine patients (14%) had discontinued sacubitril-valsartan, four patients (6%) had a dose reduction, and 17 patients (26%) had developed symptomatic hypotension. No angioedema occurred within the 12-month follow-up and there were no hospitalizations or emergency room visits within the first 14 days. Conclusions. Switching directly from target dose ACE inhibitors or ARBs to maximum-dose sacubitril-valsartan was safe and generally well tolerated.

Efficacy and safety of sacubitril-valsartan in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials

“… [31] Sacubitril-valsartan can also inhibit the activation of RAAS system, enkephalinase and the degradation of natriuretic peptide. [ 32 33 ] Sacubitril-valsartan should augment this endogenous defence mechanism and could be beneficial in heart failure with both reduced and preserved ejection fraction. [34] …”

The Efficacy and Safety of Sacubitril-Valsartan for the Treatment of Heart Failure in Adults: A Meta-Analysis

“…As Mann et al, 10 Norberg et al, 12 and Myhre et al 14 reported in their PARADIGM-HF trial, the use of SV can potentially lower the rate of hospitalization and all-cause mortality. Similarly, Voors et al 11 in their PARAMOUNT-HF trial, Velazquez et al 13 in their reported PIONEER-HF trial, Solomon et al 15 in their PARAGON-HF trial, and Desai et al 16 through their Evaluate-HF trial also reported the high therapeutic value of SV in terms of lowering atrial fibrillation, rate of myocardial infarction, and all-cause mortality.…”

“…The demographic details of the studies included in this meta-analysis [10][11][12][13][14][15][16][17][18][19] are shown in Table 1. It describes the study's author, the year it was published, the type of study, the type of trial, the duration of the study, the total sample size, the type of drug used as a control, the dose of drugs used, the age of the patients, the number of patients with positive outcomes, and the number of patients with adverse effects for statistical analysis of the data.…”

“…As Mann et al, 10 Norberg et al, 12 and Myhre et al 14 reported in their PARADIGM-HF trial, the use of SV can In line with these RCTs and other studies, like the clinical trial of Chandra et al, 20 the meta-analysis of Charuel et al, 21 and the review article of Pontremoli et al, 22 we also obtained the pooled OR of 0.80 (95% CI, 0.71-0.91) and the pooled RR of 0.92 (95% CI, 0.88-0.96) for the change in the number of patients with HF after drug intake. The OR value of less than 1 is indicative of the high efficiency of the SV in lowering the number of HF patients.…”

Sakubitril/Valsartan’ın doz titrasyonu hangi hastada nasıl yapılmalı?

“…[7][8][9] Tedavilerinde 20 mg enalapril (ya da eşdeğeri ACE-İ) veya 32 mg kandesartan (ya da eşdeğeri ARB) olan ve sistolik kan basıncı 120 mmHg'nın üzerinde bulunan hastalarda bu dozla başlamanın güvenli olduğunu gösteren bir çalışma vardır. [10] Bu doz, kılavuzlar tarafından önerilmemesi nedeni ile tedavi algoritmasında yer almayacaktır.…”